Labor induction, augmentation may be tied to autism risk

Major finding: Children born of mothers who had induced or augmented labor had 23% higher odds of being diagnosed as having autism than were those whose mothers did not have labor induction or augmentation, with ORs of 1.10 for induced labor and 1.15 for augmented labor.

Data source: A population-based epidemiologic study involving 625,042 live births in which 5,648 children were diagnosed as having autism.

Disclosures: This study was funded in part by the U.S. Environmental Protection Agency. No financial conflicts of interest were reported.



Children born after induced or augmented labor appear to be at higher risk of autism than were those born after nonaugmented labor, according to a report published online August 12 in JAMA Pediatrics.

This association, discovered in a statewide population-based epidemiologic study involving over 625,000 live births, was stronger among boys than girls. It persisted after the data were adjusted to account for known risk factors for autism including fetal distress, meconium staining, preterm delivery, and maternal diabetes, which indicates that the association is robust.

"This study also confirmed previously documented risk factors for autism such as advanced maternal age and maternal education, parity, and singleton birth," further reinforcing the strength of the data, said Simon G. Gregory, Ph.D., of the Duke Center for Human Genetics, Durham N.C., and his associates.

They cautioned that "our results are not sufficient to suggest altering the standard of care regarding induction or augmentation," both of which are known to reduce neonatal mortality; risks for neonatal ventilation, sepsis, and ICU admission; the incidence of meconium aspiration syndrome; rates of cesarean delivery; and maternal mortality. However, the findings do suggest that further research of this issue is warranted, the investigators said.

"...Our results are not sufficient to suggest altering the standard of care regarding induction or augmentation."

"It remains unclear whether (1) the act of labor induction/augmentation itself or the medications used underlie the association; (2) the medical and obstetric conditions that are associated with labor induction/augmentation drive the association; or (3) acute intrapartum events that are more common among women with labor induction/augmentation drive the association with autism," the researchers wrote.

Dr. Gregory and his colleagues used data from a state birth registry to identify the records of 625,042 live births in North Carolina during 1990-1998, which included information on maternal characteristics, labor, delivery, and neonatal factors. They linked these data with school records 7-18 years later that identified 5,648 children diagnosed as having autism.

The rates of autism in the study population were 1.3% among boys and 0.4% among girls, which are consistent with rates reported in the literature for other populations. In particular, the approximately fourfold higher incidence of the disorder among boys has been well documented in other populations.

In an initial analysis of the data, the percentage of induced and/or augmented labors was significantly higher among autistic children than among those without autism.

In addition, children with autism were more likely to have experienced fetal distress and to have had meconium staining of the amniotic fluid. The researchers intended to assess whether placental abruption and cord prolapse were associated with autism, but the small number of cases, particularly among baby girls, precluded any such analysis.

In the next data analysis, children born of mothers who had induced or augmented labor had 23% higher odds of being diagnosed as having autism than were those whose mothers did not have labor induction or augmentation. The odds ratios (OR) were 1.10 for induced labor and 1.15 for augmented labor.

A further analysis adjusted for numerous potential confounders related to socioeconomic status, maternal health, and pregnancy-related events. The odds ratios remained essentially unchanged.

An analysis that included the year of the child’s birth shifted the ORs slightly, so that "compared with the reference group, a child whose mother was both induced and augmented at delivery had 27% higher odds of being diagnosed as having autism. The ORs for the induced-only and augmented-only categories indicated an approximate 13% to 16% increase in the odds of autism, respectively," Dr. Gregory and his associates said (JAMA Pediatr. 2013 [doi:10.1001/jamapediatrics.2013.2904]).

In this analysis of the data, fetal distress raised the odds of an autism diagnosis 25%, and meconium staining raised the odds 22%. Compared with term birth, very preterm birth raised the odds 25%, and compared with no maternal diabetes, maternal diabetes raised the odds 23%. Other factors that elevated the odds of an autism diagnosis to a lesser degree included black race/ethnicity, primiparity, older maternal age, and higher maternal education level.

When the data were categorized by the child’s sex, the relationship between induction and/or augmentation and autism was found to be much stronger in boys. "Male children born to mothers who received both induction and augmentation had a 35% higher odds of autism diagnosis than the reference group," the investigators said.

These findings did not change appreciably in two sensitivity analyses.

Although this study was not designed to examine possible reasons for the association between induced/augmented labor and autism, the researchers noted that exposure to exogenous oxytocin (the usual means of inducing and augmenting labor) may contribute to the association. "Biologically, oxytocin signaling plays important prosocial roles influencing social behavior and cognitive function, and displays sexually dimorphic roles in brain function and development," they noted.

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